During natural behavior, the different ocular motor subsystems work in concert to direct gaze at object of interest. The goal of the proposed research is to learn more about abnormalities of coordination between different ocular motor subsystems in disorders of human brain. The research strategy is to 1) study natural behaviors in health, such as saccade-vergence interaction or lid-eye coordination; 2) apply new knowledge of neurophysiology in primates to understanding of human pathophysiology. The proposal has five aims. The first project deals with disconjugate adaptation of saccades in normal subjects and the role of vergence in it. The second project concerns saccade-vergence interactions in patients with cerebellar and brainstem disease. The hypothesis to be tested is that vergence system or its cerebellar projections are important for generation of disconjugate saccades. The third project is an investigation of static and dynamic horizontal alignment in patients with midbrain lesions, e.g. dorsal tectal syndrome. Quantitative studies of impaired abduction in such patients are lacking. It may reflect either increased vergence gain, or loss of a conjugate excitatory signal. Relative contribution of these mechanisms has to be clarified. The fourth project is a study of vergence and horizontal alignment in patients with internuclear ophthalmoplegia (INO). Animal studies have demonstrated increased vergence gain in experimental INO. The existence of similar phenomenon in human INO and its effects on horizontal alignment need to be examined. The fifth project investigates coordination of vertical eye and eyelid movements in patients with Parkinson's disease. Disruption of normal lid-eye synkinesis reflects structural or physiological midbrain dysfunction; vergence may contribute to it. Clinical aspects of this phenomenon are insufficiently documented; moreover, it has never been quantitatively studied, and requires better characterization. Comparing lid and eye movements, and studying vergence in patients with Parkinson's disease before and after pallidotomy may shed light on the neural substrate of lid-eye coordination. Thus, these projects will provide: (1) new information on the pathophysiological mechanisms of common ocular motor disorders, such as dorsal midbrain syndrome and INO; (2) characterization of impaired lid- eye coordination in extrapyramidal conditions; (3) better understanding of the neural substrate underlying interactions within the human ocular motor system in disease and health.